Therapeutic efficacy of N-cholinolitic drug N,N-Diethyl-5,5-diphenyl-2-pentynylamine in models of non-cardiogenic pulmonary edema

Abstract

The existing non-cardiogenic pulmonary edema (NCPE) treatment methods are not sufficiently effective. N,N-Diethyl-5,5-diphenyl-2-pentynylamine hydrochloride (DDPA), the N-cholinolitic drug, is of interest as a potential remedy for treatment of toxic pulmonary edema (TPE). The study was aimed to determine therapeutic efficacy of the drug in animal TPE models. TPE in white rats was induced through intraperitoneal thiourea injection or nitrogen dioxide inhalation. Treatment of animals involved inhalation of the DDPA aqueous solution. The efficacy was estimated based on the animals’ survival rate and lung gravimetry data. The results were assessed based on descriptive statistics using the Student's t-test. In the model of thiourea-induced NCPE, the drug administered after the toxic exposure increased the animals’ survival rate and significantly decreased lung hydration levels (149% vs. 262.5% in non-treated animals). In the model of nitrogen dioxideinduced NCPE, the drug significantly increased the rats’ survival rate within the period between 0 and 5 h, however, the differences became non-significant within 24 h. The treated animals had 15–20% lower respiratory rate and pulmonary coefficients than non-treated animals 5 h after the NO2 exposure. The use of DDPA improved the survival rate and overall health in both TPE models, however, the thiourea-based model showed better treatment outcomes compared to the NO2–based model. Such differences can be explained by the deeper and more disruptive nature of the lung tissue injury caused by nitrogen dioxide compared to that caused by thiourea. Thus, the use of DDPA in individuals with injuries induced by pulmonotoxic chemicals may be promising at the prehospital stage.